Background: This Fast Fact reviews the evidence for corticosteroids which are often prescribed to address symptoms common to patients with terminal illnesses (1).

Pharmacology: Dexamethasone is often selected in palliative care given its prolonged half-life, multiple routes of administration, and relatively low mineralocorticoid effect (thus less likelihood of fluid retention) (2). Prednisone, prednisolone, and methylprednisolone may be acceptable alternatives depending on the clinical circumstance. Prednisone is converted by liver enzymes to the active compound prednisolone. Therefore, prednisolone or methylprednisolone are preferred in liver impairment (3). 

Adverse Effects: Although the risk of adverse effects increases with dose and duration of any corticosteroid, long-term treatment (e.g. longer than a month) with relatively low doses (defined as a prednisone 5 mg or less) is generally well tolerated (4).

• Early adverse effects (seen in days):  hyperglycemia, fluid retention, and mental disturbances (insomnia, agitation, euphoria, paranoia, see Fast Fact #323). 
• Late adverse effects (weeks to months): myopathy leading to proximal limb muscle weakness and reduced respiratory force; infection risk (especially fungal such as oral thrush); additive risk of GI bleed with NSAIDS (5). Proton pump inhibitors and/or H2 antagonists are likely only needed for daily doses of ≥ 140 mg of dexamethasone or those taking concomitant NSAIDs (6).

Considerations when prescribing corticosteroids:

• Monitor regularly. Aim to discontinue corticosteroids within 5–7 days if there is an insufficient clinical response. Doing so can prevent the need to reduce the dose gradually (taper).
• Aim for the lowest therapeutic dose to prevent side effects. If taking ≤ 4 mg of dexamethasone (or its equivalent) for 3 weeks or less, it is likely safe to stop steroids abruptly without a taper (4).
• Unless an emergency, most corticosteroids can be administered once daily in the morning, or twice daily with the last dose before 2:00 pm. This dosage schedule reduces suppression of the hypo-pituitary-adrenal axis and the risk of insomnia (3). 
• Consider prognosis. Side-effects become a cumulative problem when prognosis is months or more.
• Monitor for hyperglycemia, especially in patients with an anticipated prognosis of months or more.
• Consult the primary oncologist before starting corticosteroids, as they may impact the effectiveness of immune-based systemic cancer treatments.

Glucocorticoid (3,7,8)	Dose Equivalent	Available Routes	Common Dosage	Weekly Cost* (US $)
Prednisone	4-6 mg	PO	5-40 mg/day in 1-2 doses	$5-10
Prednisolone	5 mg	PO solution	5-60 mg/day in 1-2 doses	$20-45
Methyl-prednisolone	8 mg	IV, IM, PO	4-8 mg QID (oral); 40-125 mg/day in 1-2 doses (IV/IM)	$10-35
Dexamethasone	0.75 mg	PO, IV, IM, SQ	2-8 mg/day in 1-2 doses	$5-50

*Approximate weekly cost of generic version of the most common prescribed PO dose.

Symptom (Suggested dexamethasone dose) (2,6,9)	Supporting clinical evidence in palliative care
Cancer Related Fatigue (CRF):(2-4 mg a day)	CRF and quality of life (QOL) benefits noted via improvements in Functional Assessment of Chronic Illness-Fatigue (FACIT-F) total QOL and subscale scores at day 15 of administration compared to placebo (10).
Nausea and Vomiting  (4-8 mg a day)	Dexamethasone can prevent chemotherapy-induced nausea and vomiting, especially when combined with ondansetron or granisetron (11-13). There is only low-quality evidence supporting its effectiveness for nausea or vomiting unrelated to chemotherapy (14).
Anorexia and Cachexia(2-4 mg a day)	Dexamethasone may improve appetite in 68.5% of palliative care patients after a 7-day treatment course (15). Methylprednisolone may improve appetite in up to 77% of terminally ill patients after a 14-day course (16).
Dyspnea(4-8 mg a day)	There is mixed evidence for dexamethasone or prednisone to relieve dyspnea in patients with a terminal illness (17). There is no supporting evidence for methylprednisolone to prevent or relieve dyspnea in the terminally ill. Many clinicians target corticosteroid use to those with emphysema or asthma.
Pain(8 mg a day)	Dexamethasone is commonly prescribed for cancer-related bone pain, neuropathic pain, liver capsular pain, and radiation-induced pain (18,19). While dexamethasone and methylprednisolone have been shown to decrease patients’ numeric pain score (most substantially for radiation-induced pain flares), the results have not always been significant (18-20).
Malignant bowel obstruction (MBO)(8 mg a day)	Literature on the effectiveness of dexamethasone to alleviate MBO or the symptoms associated has offered mixed results (21). There is no convincing evidence for the use of methylprednisolone to prevent or treat MBO.
Metastatic Extradural Spinal Cord Compression (MESCC)(10 mg IV x1; then 16 mg/day)	The evidence supporting dexamethasone to reduce pain and improve function from MESCC is promising but limited (22,23). See Fast Fact #238 for details on MESCC management.  There is no supporting evidence for prednisone or methylprednisolone in those with a terminal illness and MESCC.
Other Urgent Palliative Care Conditions(10 mg IV x 1; then 16 mg/day)	Experts suggest similar dexamethasone dosing to palliate symptoms related to malignancy-induced intracranial pressure, superior vena cava syndrome, tracheal obstruction, and lymphangitis carcinomatosis; however, there is no controlled data for these indications.

References

1. Shih A, Jackson KC. Role of Corticosteroids in Palliative Care. Journal of Pain & Palliative Care Pharmacotherapy. 2007;21(4):69-76. doi:10.1080/J354v21n04_14
2. Twycross R, Wilcock A. (editors). Palliative Care Formulary. 3rd edition. Nottingham. Palliativedrugs.com. Ltd 2007; p.362-368.
3. Ericson-Nielsen W. Steroids: Pharmacology, Complications, and Practice Delivery Issues. Ochsner J. 2014 Summer; 14(2): 203–207.
4. Mundell L, et al. Monitoring Long-Term Oral Corticosteroids. BMJ Open Quality 2017;6:e000209. doi:10.1136/bmjoq-2017-000209 1.
5. Piper JM, Ray WA, Daugherty JR et al. Corticosteroid use and peptic ulcer disease: role of nonsteroidal anti-inflammatory drugs. Ann Intern Med 1991;114:735–740.
6. Ellershaw JE, Kelly MJ. Corticosteroids and peptic ulceration. Palliat Med 1994; 8(4): 313-319.
7. Mager DE, Lin SX, Blum RA, Lates CD, Jusko WJ. Dose equivalency evaluation of major corticosteroids: pharmaokinetics and cell trafficking and cortisol dynamics. J Clin Pharmacol. 2003 Nov. 43(11):1216-27.
8. Corticosteroids.  www.goodrx.com.  Last accessed February 18, 2020
9. Back I. Palliative Medicine Handbook. 3rd Ed 2001 p126-129.
10. Yennurajalingam S, Frisbee-Hume S, Palmer JL, Delgado-Guay MO, Bull J, Phan AT, Tannir NM, Litton JK, Reddy A, Hui D, Dalal S, Massie L, Reddy SK, Bruera E. J Clin Oncol. 2013;31(25):3076. Epub 2013 Jul 29.
11. Italian Group for Antiemetic Research. Dexamethasone, granisetron, or both for the prevention of nausea and vomiting during chemotherapy for cancer. N Engl J Med. 1995;332(1):1-5. doi:10.1056/NEJM199501053320101
12. Italian Group for Antiemetic Research. Dexamethasone alone or in combination with ondansetron for the prevention of delayed nausea and vomiting induced by chemotherapy. N Engl J Med. 2000;342(21):1554-1559. doi:10.1056/NEJM200005253422102
13. Inoue A, Yamada Y, Matsumura Y, et al. Randomized study of dexamethasone treatment for delayed emesis, anorexia and fatigue induced by irinotecan. Support Care Cancer. 2003;11(8):528-532. doi:10.1007/s00520-003-0488-y
14. Vayne-Bossert P, Haywood A, Good P, Khan S, Rickett K, Hardy JR. Corticosteroids for adult patients with advanced cancer who have nausea and vomiting (not related to chemotherapy, radiotherapy, or surgery). Cochrane Database Syst Rev. 2017;7:CD012002. doi:10.1002/14651858.CD012002.pub2
15. Yavuzşen T, Davis MP, Walsh D, Legrand SB, Lagman R. Systematic review of the treatment of cancer-associated anorexia and weight loss. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2005;23(33):8500-8511. doi:10.1200/JCO.2005.01.8010
16. Bruera E, Roca E, Cedaro PL, Carrara S, Chacon R. Action of oral methylprednisolone in terminal cancer patients: a prospective randomized double-blind study. Cancer Treat Rep. 1985;69(7-8):751-754.
17. Maeda T, Hayakawa T. Effectiveness of Corticosteroid Monotherapy for Dyspnea Relief in Patients with Terminal Cancer. Journal of Pain & Palliative Care Pharmacotherapy. 2017;31(2):148-153. doi:10.1080/15360288.2017.1301618
18. Barghi K, Edmonds KP, Ajayi TA, Atayee RS. Prescribing Trends of Palliative Care Team’s Use of Dexamethasone for Cancer-Related Pain. Journal of Pain & Palliative Care Pharmacotherapy. 2018;32(1):37-43. doi:10.1080/15360288.2018.1460436
19. Lussier D, Huskey A, Portnoy R. Adjuvant Analgesics in Cancer Pain Management. The Oncologist September 2004   vol. 9  no. 5  571-591. doi: 10.1634/theoncologist.9-5-571
20. Chow E, Meyer RM, Ding K, et al. Dexamethasone in the prophylaxis of radiation-induced pain flare after palliative radiotherapy for bone metastases: a double-blind, randomised placebo-controlled, phase 3 trial. The Lancet Oncology. 2015;16(15):1463-1472. doi:10.1016/S1470-2045(15)00199-0
21. Feuer DJ, Broadley KE. Systematic review and meta-analysis of corticosteroids for the resolution of malignant bowel obstruction in advanced gynaecological and gastrointestinal cancers. Ann Oncol. 1999;10(9):1035-1041. doi:10.1023/A:1008361102808
22. Sørensen S, Helweg-Larsen S, Mouridsen H, Hansen HH. Effect of high-dose dexamethasone in carcinomatous metastatic spinal cord compression treated with radiotherapy: a randomized trial. Eur J Cancer. 1994;30A(1):22-27. doi:10.1016/s0959-8049(05)80011-5
23. George R, Jeba J, Ramkumar G, Chacko AG, Tharyan P. Interventions for the treatment of metastatic extradural spinal cord compression in adults. Cochrane Database Syst Rev. 2015 Sep 4;(9):CD006716. doi: 10.1002/14651858.CD006716.pub3.

Authors’ Affiliations: Montefiore Medical Center, Albert Einstein College of Medicine. Bronx, NY. Conflicts of Interest: None

Version History:  Originally edited by Sean Marks MD; first electronically published in April 2020.

Acknowledgments:  We would like to thank Linnea Jurs, a student at the University of North Carolina at Chapel Hill, for her writing and editing assistance.